COMPOSITE PHEOCHROMOCYTOMA GANGLIONEUROMA OF THE ADRENAL-GLAND ASSOCIATED WITH MULTIPLE ENDOCRINE NEOPLASIA 2A - CASE-REPORT WITH IMMUNOHISTOCHEMICAL ANALYSIS/

We report a case of composite pheochromocytoma/ganglioneuroma arising in a background of diffuse and nodular medullary hyperplasia in the ad renal gland of a 34-year-old man with multiple endocrine neoplasia 2a (MEN 2a). Cells were histologically classified as chromaffin or chroma ffin-like (small typical-appearing pheochromocytoma cells), neuron-lik e (possessing ganglion cell morphology), and intermediate. We speculat e that these cell types may represent a spectrum of differentiation of a neoplastic clone, with the intermediate cells representing a transi tional stage between chromaffin cells and neurons. All three cell type s in the composite tumor and all chromaffin cells in both nodular and nonnodular areas of the remaining medulla were strongly immunoreactive for tyrosine hydroxylase, the rate-limiting enzyme in catecholamine s ynthesis. In contrast, neuron-like cells (and to a variable extent int ermediate cells) displayed selective loss of expression of phenylethan olamine-N-methyltransferase (PNMT), the enzyme that synthesizes epinep hrine. Proliferative activity of the composite tumor and both the nodu lar and nonnodular medulla was studied by staining for the endogenous cell proliferation antigen Ki-67, using monoclonal antibody MIB-1. MIB -1 labeling was highest in Schwann cell areas of the composite tumor, followed by chromaffin-like cells in the composite tumor and in the se parate nodules. Labeling was absent in neuron-like cells, consistent w ith the cells' postulated status as terminally differentiated derivati ves of a chromaffin cell precursor, and was highly variable in nonnodu lar areas of the medulla. The latter observation suggests topographica l variation in signals that drive chromaffin cell proliferation in MEN .